Abstract Number: PB0467
Meeting: ISTH 2021 Congress
Theme: Hemophilia and Rare Bleeding Disorders » Hemophilia - Basic
Background: Mechanisms of VWF in vessel wall and platelet interactions are well documented. In addition, VWF also modulates plasma coagulation and fibrinolysis.
Aims: We evaluated the effects of VWF in plasma ROTEM, in standard one-stage clotting assay and in plasma clot growth with the Thrombodynamics (Hemacore).
Methods: APTT was with silica reagent. Rotem analysis after recalcification recorded maximal clot firmness; with thrombodynamics both growth of fibrin and formation of thrombin was followed. Deficient plasma’s for VWF and Factor VIII, and normal plasma were obtained from commercial sources. Added VWF was Willefact.
Results: With normal physiological concentrations, factor VIII is approximately for 50% reversibly bound to VWF. In the complex, Factor VIII clotting activity is inhibited. Assay with APTT shows about 2-fold higher Factor VIII when VWF is absent. This was used for a modification of factor analysis with lower detection limit valuable in severe haemophilia patients.
In the thrombodynamic system, no effect was observed on thrombin generation at the tissue factor surface and on the rate of clot growth from 0-100% VWF. However, a clear increase in thrombin generated further away from the surface (intrinsic thrombin generation dependent upon factor XI, IX and VIII) was seen with an increase in thrombin amplitude of 250% for 100 – 0% VWF. This thrombin formation is considered to produce increased thrombomodulin (TM)-dependent TAFI activation and concerns a potential of clot protection against lysis in TM-rich area’s in VWF deficiency.
ROTEM recalcifation analysis of VWF deficient plasma shows a low rigidity, which increases dose-dependently after addition of VWF.
Conclusions: Taken these effects together it suggests that plasma coagulation in VWF deficiency results in relatively more rapid coagulation due to larger effects of factor VIII, more clot stabilization in TM-rich environment, and a lower rigidity. These opposite effects may modulate the bleeding profile.
To cite this abstract in AMA style:
Kluft C, Van Leuven K, Krijnen C, De Kruijf P. Effects of von Willebrand Factor on Plasma Haemostasis [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/effects-of-von-willebrand-factor-on-plasma-haemostasis/. Accessed November 29, 2021.« Back to ISTH 2021 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/effects-of-von-willebrand-factor-on-plasma-haemostasis/